Faecal Microbiota Transplant in Parkinson's Disease: Pilot Study to Establish Safety & Tolerability

Faecal Microbiota Transplant in Parkinson's Disease: Pilot Study to Establish Safety & Tolerability | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Faecal Microbiota Transplant in Parkinson's Disease: Pilot Study to Establish Safety & Tolerability Michele De Sciscio, Robert V Bryant, Sarah Haylock-Jacobs, Alice S Day, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6190300/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Jul, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted 9 You are reading this latest preprint version Abstract There is growing evidence that differences exist in the gut microbiota of patients with Parkinson’s Disease (PD) compared with health controls, and so treatment with Faecal Microbiota Transplantation (FMT) may provide a novel approach towards altering disease progression and response to treatment. We performed a pilot study looking at the safety and tolerability of FMT, its effect on the microbiome, and improvement of symptoms in PD. This was an open label study wherein 12 patients with mild to moderate PD were administered FMT via enema for 6 months. The primary objectives were safety and tolerability of therapy as well as changes in motor and non-motor symptoms of PD. FMT administered as liquid enema was safe and well tolerated, associated with mild and self-resolving gastrointestinal symptoms. We found no significant change in motor outcomes post FMT however showed a trend towards improvement in daily OFF time after 2 months of treatment. We found no significant improvement in non-motor symptoms of PD after 6-months of FMT, however showed improvement in quality of life and non-motor symptom scores at 2 months as well as a trend towards improvement in parts 1 and 2 of the MDS-UPDRS. All improvements regressed back to baseline after 6 months of treatment. The administration of FMT over an extended 6-month period for the treatment of mild to moderate PD is safe and tolerable. FMT was associated with a transient reduction in daily motor OFF time as well as multiple self-reported non-motor symptoms. Health sciences/Diseases/Neurological disorders/Movement disorders/Parkinsons disease Biological sciences/Neuroscience/Motor control/Basal ganglia Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Parkinson’s Disease (PD) is characterized by the accumulation of abnormal alpha-synuclein isoforms in neurons, causing dysfunction and cell death ( 1 ). Disease progression is thought to result from the cell-to-cell transmission of alpha-synucleinopathy, leading to neurodegeneration ( 2 ). The hallmark motor symptoms—tremor, rigidity, and bradykinesia—reflect neurodegeneration in central nervous system (CNS) motor circuits. However, evidence suggests that alpha-synuclein pathology begins in non-CNS neurons, such as those in the gut, years before affecting CNS neurons ( 3 ). The gut is increasingly recognized as a key area in PD research. Alpha-synucleinopathy affects enteric neurons early, often causing constipation as a prodromal symptom ( 4 ). Additionally, the vagus nerve may facilitate the spread of alpha-synucleinopathy from the gut to the CNS, with reduced PD risk in individuals who have undergone vagotomy and increased risk in those with inflammatory bowel disease ( 5 ). This has led to growing interest in the role of gut microbiota in PD pathogenesis. Studies show that PD patients have altered microbiota, including higher levels of pro-inflammatory bacteria, lower levels of anti-inflammatory bacteria, and reduced microbial diversity ( 6 – 8 ). Though the exact link between gut dysbiosis and PD remains unclear, it may involve increased gut permeability and alpha-synuclein seeding in enteric neurons ( 2 ). Moreover, microbiota composition correlates with motor and non-motor symptom severity and responses to dopaminergic treatments ( 9 ). Fecal Microbiota Transplantation (FMT) is emerging as a potential therapy to modulate the gut microbiota in PD. Parkinson’s Disease mouse models have shown that FMT with healthy human-derived microbes improves motor function and protects against dopaminergic neuronal death ( 10 ). However, human studies on FMT's safety and efficacy are limited to short-term trials ( 11 , 12 ). This study aims to assess the safety and tolerability of an extended 6-month FMT course in mild to moderate PD patients. We will also evaluate the impact of FMT on daily OFF time, motor and non-motor symptoms, quality of life, and changes in gut microbiota composition and function. METHODS Study Participants Twelve participants aged over 30 with a history of PD were recruited for this pilot study between June 2021 and November 2022. Key inclusion criteria were: (i) diagnosis of idiopathic PD for ≤ 10 years, as per the UK Parkinson's Disease Society Brain Bank criteria; (ii) a positive dopaminergic response, defined by a ≥ 33% reduction in Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III motor score between OFF and ON-dopaminergic medication states; and (iii) motor fluctuations with at least 2 hours of daily OFF time on at least two consecutive days. Subjects with mild cognitive impairment (Montreal Cognitive Assessment score < 26) were excluded. Participants were required to maintain stable PD therapy for 30 days before and throughout the study. Study Design This was a prospective open-label, single centre study conducted by the Neurology and Gastroenterology Units of the Central Adelaide Local Health Network, Adelaide, Australia. Subjects underwent clinical assessment at baseline (pre-FMT), and at 2- and 6-months post FMT treatment commencement. FMT Treatment Regimen FMT enemas were sourced from Biomebank, a Therapeutic Goods Administration (TGA)-accredited provider based in South Australia (ARTG #399066). The FMT donor screening, collection, and manufacturing followed the standards outlined in Therapeutic Goods Order No. 105 – Standards for FMT ( 13 ). The FMT was administered by a clinical nurse as a 50mL enema containing 12.5g of donor faeces. Subjects were instructed to retain the FMT for at least 30 minutes in the right lateral position. The intervention consisted of an induction phase with 6 donor FMT enemas over 8 weeks (weeks 0, 1, 2, 3, 5, 7), followed by a maintenance phase with 4 monthly donor FMT enemas over 4 months (months 3, 4, 5, 6), totalling 6 months of FMT therapy. Study Assessments Daily OFF time was measured using Hauser motor diaries, completed by subjects for 48 consecutive hours. Subjects rated their motor state every half hour as “on without dyskinesia,” “on with non-troublesome dyskinesia,” “on with troublesome dyskinesia,” “off,” or “asleep.” Daytime ratings were contemporaneous, and overnight scores were made retrospectively. Subjects were assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the modified Hoehn and Yahr Scale. The MDS-UPDRS includes 4 domains: Part I (non-motor aspects of daily living), Part II (motor aspects of daily living), Part III (motor examination), and Part IV (motor complications). Subjects attended baseline visits in the “OFF medication” state after overnight withdrawal of dopaminergic medication. The MDS-UPDRS Part III score was assessed in both “OFF” and “ON” medication states, approximately 1 hour after the usual morning dose of dopaminergic medication. For the 2- and 6-month visits, no pre-visit motor state stipulation was required. Motor examinations were performed by a single movement disorders specialist. Safety and tolerability were monitored through adverse event reporting, patient experience questionnaires, and visual analogue scales. Subjects completed an adverse event questionnaire at each visit. Subjects completed a 2-point Likert scale questionnaire at each visit rating FMT’s acceptability, tolerability, and safety based on preconceived opinions and during treatment. Six non-motor questionnaires were completed, including the Geriatric Depression Scale Short Form (GDS-SF), Parkinson’s Disease Questionnaire (PDQ-39), Parkinson’s Disease Non-Motor Symptoms Scale (PD NMS), Parkinson’s Disease Fatigue Scale (PFS-16), Beck Depression Inventory, and Parkinson’s Disease Sleep Scale (PDSS-2). Across the study, subjects also reported subjective changes in motor symptoms, falls, constipation, and cognitive function. Bowel function was assessed using a 7-day diary, and microbiome analysis was performed at all timepoints. Constipation was defined by the Rome IV criteria for Bowel Disorders. Subjects received dietary education from an academic dietitian at -14 days pre-FMT and at 2- and 6-month visits. They completed a 3-day weighed food diary, and data were analysed for energy, macronutrients, fibre, and micronutrients. A Safety Review Committee (SRC) comprising experts in gastroenterology (RB) and neurology (TK, MD) was established to ensure participant safety. Microbiome Analysis Stool samples were collected in OMNIGene gut tubes (DNA Genotek) and sent for shotgun metagenomic sequencing at a depth of 40M 150bp paired-end reads on a DNBseq NanoBall platform. Statistical Methods Data are presented as mean (± standard deviation) unless otherwise noted. Comparisons were analysed using a mixed-effects model to account for missing data, with Tukey’s multiple comparisons tests to compare timepoints. A p-value of < 0.05 was considered statistically significant. Dietary data were analysed using one-way ANOVA for normally distributed data. Statistical analyses were performed with GraphPad Prism version 10.0.2. A convenience sample size was used for this pilot study. Microbial makeup was profiled using standard bioinformatics tools (MetaPhlan V4), and microbiome analysis was conducted at BiomeBank, Australia to assess species richness, evenness (Pilou index), and alpha diversity (Shannon index). Microbiome indices were analyzed using a mixed-effects model with Tukey’s tests. Missing stool samples and questionnaires were handled with appropriate statistical methods. RESULTS Patient Characteristics A total of 12 subjects (8 females, 4 males; mean age 69.5 years) received FMT treatment, Table 1 . The mean disease duration was 6.9 years, and all were on L-dopa therapy ± adjunctive dopaminergic treatments, with a mean daily L-dopa equivalent dose of 684mg (range 100-1300mg). Key clinical markers of PD severity included: (i) daily OFF time (mean 4.8 hrs/24hrs, SD 2.2), (ii) UPDRS Part 3 in the OFF state (mean 28.3, SD 12.5) and ON state (mean 12.7, SD 8.3), and (iii) total UPDRS score (mean 42.8, SD 15.5). Constipation was reported in 58% of patients, with 9 of 12 subjects (75%) meeting the Rome IV criteria for functional constipation based on baseline 7-day bowel diaries. Table 1: Patient Demographics and Baseline Values Baseline Characteristics n=12 Male Patients 8 (66%) Age at enrolment (years) 69.5 (4.3) Age at diagnosis (years) 62.6 (5.7) BMI 25.0 (5.6) Disease duration at enrolment, (years) 6.9 (2.4) Medications L-dopa equivalent daily dose (mg) Dopamine agonist Monoamine oxidase inhibitors COMT inhibitors 684 (431) 8 (67%) 7 (58%) 4 (33%) Comorbidities Diabetes Hypertension Depression Anxiety 2 (17 %) 3 (25 %) 4 (33 %) 5 (42 %) Parkinson’s symptoms Tremor Rigidity Akinesia/Bradykinesia Freezing of gait Constipation 10 (83 %) 11 (92 %) 12 (100 %) 3 (25 %) 7 (58 %) Montreal Cognitive Assessment 27.3 (1.3) Parkinson’s Disease Severity Metrics UPDRS 1 UPDRS 2 UPDRS 4 UPDRS 3: OFF-state UPDRS 3: ON-state Hauser Motor Diary (OFF time/24hrs) 2.3 (1.6) 21.4 (8.0) 6.3 (1.8) 28.3 (12.5) 12.7 (8.3) 4.8 (2.2) Data expressed as either mean (SD), or number of patients (%). BMI=Body Mass Index; COMT=catechol-O-methyltransferase; UPDRS = Unified Parkinson’s Disease Rating Scale. * Constipation determined according to the Rome IV Criteria for Colonic Disorders Primary Endpoints Safety & Tolerability All subjects who received at least one dose of FMT were included in the safety analysis. Eleven of 12 subjects (92%) completed the full 6-month treatment course. One serious adverse event (SAE) occurred: a subject was hospitalized with worsening motor symptoms after 2 months of treatment and withdrew from the study. The SAE was deemed unlikely to be related to FMT, as the subject had a history of steady functional decline prior to enrolment. Gastrointestinal adverse events were reported by 10 of 12 subjects (83%) as ‘probably’ or ‘definitely’ related to FMT, Table 2 . These events were transient and mild, mostly occurring during the induction phase. No treatments were withheld due to adverse events. The most common adverse events were increased flatulence (50%), abdominal pain (42%), constipation (42%), and bloating (42%). Table 2 Self-reported adverse events throughout 6 months of therapy deemed “probably” or “definitely” related to FMT Adverse event Number of Patients (%) Nausea 3 (25%) Bloating 5 (42%) Abdominal pain/cramping 4 (33%) Diarrhoea 3 (25%) Constipation 7 (58%) Increased flatulence 6 (50%) Using a 100-point visual analogue scale, most patients rated the acceptability and safety of FMT highly, with scores above 70/100 in 11 of 12 patients at both 2 and 6 months, Fig. 1 . Secondary Endpoints Efficacy of FMT on Motor Function The mean self-reported daily OFF-time (averaged over 48 hours) was 4.8 hours/day (SD 2.2) at baseline and reduced to 3.8 hours/day (SD 1.8) after 2 months (p = 0.58). However, this reduction was not sustained, with daily OFF-time returning to baseline levels by 6 months (4.4 hours/day, SD 2.8), Fig. 2 . There was no significant change in UPDRS-Part IV scores, assessing motor complications, from baseline (6.3, SD 1.8) to 2 months (6.7, SD 1.8) and 6 months (5.6, SD 3.0) (p = 0.49). Most subjects (7/12) attended their 2- and 6-month reviews in a motor ON-state, allowing comparisons of ON-state MDS-UPDRS III (motor examination) scores across all three timepoints. While there was no improvement in these scores (baseline 9.4, SD 5.2; 2 months 9.7, SD 6.2; 6 months 9.7, SD 6.2; p = 0.873), there was also no deterioration in the mean MDS-UPDRS III score over the 6-month treatment period, Fig. 2 . Efficacy of FMT on Non-Motor Function After two months of FMT therapy, there was a non-significant reduction in the mean UPDRS Part I score (baseline 2.3, SD 1.6 vs 2 months 1.5, SD 1.5; p = 0.336, 35% reduction) and UPDRS Part II score (baseline 21.4, SD 8.0 vs 2 months 17.9, SD 9.8; p = 0.089, 16% reduction), Fig. 2 . This reduction was maintained at 6 months for UPDRS Part II (17.1, SD 6.2), but UPDRS Part I showed regression towards baseline (1.8, SD 1.6). There was a statistically significant reduction in PDQ-39 scores between baseline and 2 months (34.7, SD 15.8 vs 25.3, SD 13.2; p = 0.032) and a trend towards a reduction in NMSQ scores (9.5, SD 4.3 vs 7.7, SD 3.4; p = 0.163), Fig. 3 . However, these improvements were not maintained at 6 months. No statistically significant changes were observed in PFS-16, PDSS-2, BDIS, GDS, or PDSS-2 scores after 2 or 6 months of treatment. Efficacy of FMT on Bowel Function There was no improvement in bowel-related symptoms, as assessed by the 7-day bowel diary, after 2 or 6 months of FMT therapy. However, fewer subjects met the Rome IV criteria for functional constipation at 6 months post-treatment (baseline 9/12 [75%] vs 6 months 7/11 [64%]). Dietary optimisation and adequacy during FMT Therapy Before receiving FMT, subjects' habitual diets were inadequate in dietary fibre and resistant starch, with a higher total protein intake. After individualized dietary advice, there was a trend toward increased dietary fiber at 8 weeks (mean intake 28.2g/d ± 9.98g/d), but this was not sustained at 24 weeks (24.7g/d ± 9.55g/d). Three subjects (27%) declined to modify their diet, and three (27%) chose to follow a gluten-free diet. Microbiome Changes with FMT Therapy There was no difference in alpha diversity (Shannon index), richness, or evenness (Pilou index) of the gut microbiome from baseline in patients treated with FMT for 2 and 6 months. While minor changes were observed in some individual patients, most reverted to baseline by month 6, and aggregated results were non-significant, indicating no overall changes throughout the study. DISCUSSION This is the first study to evaluate the safety and tolerability of a 6-month FMT enema therapy course in patients with mild to moderate PD, showing that FMT is safe and well-tolerated. Apart from one serious adverse event (SAE) unrelated to FMT, adverse events were mild, self-limiting, and did not lead to treatment discontinuation. Most subjects rated FMT as safe and tolerable. These safety findings align with two recent studies that administered FMT to PD patients via oral capsules or colonic/nasointestinal routes. While gastrointestinal side effects were common, all were mild and self-limiting. FMT therapy for various gastrointestinal indications in 4,241 patients has been shown to be highly safe, with only mild or moderate adverse events ( 14 ). Although this study was not designed to assess efficacy, there was a significant improvement in QOL scores at 2 months post-FMT. Additionally, trends toward improvement were observed in non-motor scales, including the non-motor symptom questionnaire (NMSQ), UPDRS Parts I & II, and PDSS-2 scores, but these were not sustained at 6 months. A trend toward improvement in motor symptoms was observed, with a reduction in self-reported OFF-time at 2 months (mean 4.8hrs/day at baseline vs. 3.8hrs/day at 2 months), corresponding to a 21% reduction. Although this improvement was not statistically significant or sustained at 6 months, motor impairment scores (Hauser diary OFF-time and ON-state MDS-UPDRS motor examination score) at 6 months were at or slightly improved compared to baseline. To our knowledge, this is the first study to assess the effects of FMT on daily OFF-time in PD, using the Hauser motor diary, which is increasingly favoured in PD to more accurately represent real-world motor dysfunction in daily life. The initial improvement in PDQ-39 and trend towards improvement in NMSQ scores, at 2 months, coinciding with the induction phase of therapy (weekly or fortnightly FMT enemas), suggests that more frequent dosing may be needed to sustain benefits. This aligns with a recent placebo-controlled study where greater improvement was seen with more frequent FMT dosing ( 11 ). However, another study showed significant improvement in non-motor symptoms with a single colonic or nasogastric FMT, suggesting a single dose may also be effective ( 12 ). While no significant improvement in bowel symptoms (7-day bowel diary) was seen, a reduction in subjects meeting the Rome IV criteria for functional constipation was noted at 6 months (75% at baseline vs. 64% at 6 months). Previous studies have demonstrated improvements in constipation with FMT, including changes in bowel transit and motility index, potentially due to increased gut microbiome diversity. Our study did not show significant changes in alpha diversity, richness, or evenness of the gut microbiome, possibly due to the enema delivery method and frequency of dosing. This study has several limitations. It was an open-label, non-randomized pilot with a small sample size, limiting its ability to detect significant effects. Furthermore, despite regular dietetics input, many subjects maintained inadequate fibre and resistant starch intake, which may have affected FMT engraftment and minimized potential benefits. Finally, our study was a convenience sample of patients referred by their Movement Disorder Specialist, many of which were aware of FMT as a potential therapy for PD. Thus, our study may not be representative of the broader population of patients with PD. Despite these limitations, this pilot study suggests the potential clinical value of FMT in PD and justifies further investigation through larger, double-blind, placebo-controlled trials with oral, daily FMT dosing. CONCLUSION This study demonstrated that a 6-month course of FMT for treating mild to moderate PD is safe and well-tolerated. FMT was associated with improvements in self-reported quality of life and trends toward reductions in daily OFF-time and multiple non-motor symptoms. However, these benefits were most apparent with more frequent FMT dosing, with regression toward baseline observed with less frequent therapy. The findings are promising and support further investigation into FMT as a novel and safe treatment option for PD management. Declarations ETHICAL COMPLIANCE STATEMENT Procedures involving experiments on human subjects are done in accordance with the ethical standards of the Committee on Human Experimentation of the institution in which the experiments were done or in accord with the Helsinki Declaration of 1975. All participants provided written consent to participate in this study. The study was approved by Central Adelaide Local Health Network Human Research Ethics Committee (# 2021/HRE00012). FUNDING This study was funded by the Hospital Research Foundation Group (2021/23-QA253). ACKNOWLEDGEMENTS We acknowledge the efforts of the Queen Elizabeth Hospital Inflammatory Bowel Disease Clinical Trial Nurses who were involved in the administration of FMT and post-treatment care of patients throughout the duration of the study. DATA SHARING The data that support the findings of this study are available from the corresponding author upon reasonable request. References Jankovic J, Tan EK (2020) Parkinson’s disease: etiopathogenesis and treatment. Journal of Neurology, Neurosurgery & Psychiatry 91, 795-808. Fitzgerald E, Murphy S, Martinson HA (2019) Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson's Disease. Front Neurosci . 24, 13:369. doi: 10.3389/fnins.2019.00369. PMID: 31068777; PMCID: PMC6491838. 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Disord . 30, 350–358. doi: 10.1002/mds.26069 Schwiertz, A. et al (2018) Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson’s disease. Parkinsonism Relat. Disord . https:// doi.org/10.1016/j.parkreldis.2018.02.022 Unger, M.M.,Spiegel, J.,Dillmann, K (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism Relat Disord 32, 66–72. Baldini F, Hertel J, Sandt E, Thinnes CC, Neuberger-Castillo L, Pavelka L, et al (2020) Parkinson’s disease-associated alterations of the gut microbiome predict disease- relevant changes in metabolic functions. BMC Biol 18:62. doi: 10.1101/691030 Sun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, et al (2018) Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson’s disease mice: gut microbiota, glial reaction and TLR4/TNF-alpha signaling pathway. Brain Behav Immun . 70, 48–60. doi: 10.1016/j.bbi.2018.02.005 DuPont HL, Suescun J, Jiang ZD, Brown EL, Essigmann HT, Alexander AS, DuPont AW, Iqbal T, Utay NS, Newmark M, Schiess MC (2023) Fecal microbiota transplantation in Parkinson's disease-A randomized repeat-dose, placebo-controlled clinical pilot study. Front Neurol . 2;14:1104759. doi: 10.3389/fneur.2023.1104759. PMID: 36937520; PMCID: PMC10019775. Xue LJ, Yang XZ, Tong Q, Shen P, Ma SJ, Wu SN, Zheng JL, Wang HG (2020) Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study. Medicine (Baltimore) . 28;99(35):e22035. doi: 10.1097/MD.0000000000022035. PMID: 32871960; PMCID: PMC7458210. Tucker EC, Haylock-Jacobs S, Rapaic M, Dann LM, Bryant RV, Costello SP (2023) Stool donor screening within a Therapeutic Goods Administration compliant donor screening program for fecal microbiota transplantation. JGH Open . 21;7(3):172-177. doi: 10.1002/jgh3.12874. PMID: 36968571; PMCID: PMC10037028. Marcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F (2021) Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. AP&T . 53:1 33-42. https://doi.org/10.1111/apt.16148 Additional Declarations Competing interest reported. RV Bryant and SP Costello are shareholders in BiomeBank. However, the research was performed in keeping with good clinical practice with appropriate governance and oversight (including a safety monitoring board) to mitigate this conflict. Cite Share Download PDF Status: Published Journal Publication published 09 Jul, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted Editorial decision: Revision requested 14 Apr, 2025 Reviews received at journal 09 Apr, 2025 Reviews received at journal 20 Mar, 2025 Reviewers agreed at journal 20 Mar, 2025 Reviewers agreed at journal 19 Mar, 2025 Reviewers invited by journal 18 Mar, 2025 Editor assigned by journal 17 Mar, 2025 Submission checks completed at journal 17 Mar, 2025 First submitted to journal 09 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6190300","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":433304103,"identity":"c4560ab7-f8b2-41fc-96cf-7c35fa977f20","order_by":0,"name":"Michele De Sciscio","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIie2RMUvDQBTH/6VwWY5mvaDkGwgngegQ4lfJUch0Q0fHm9olOAt+CT9CIEOWgGvFwYZCujjELciBHqFDhaTaTeR+8OAdvB9/3j3AYvmLTEGAhWlyUwlA4ajfKPxQofmPOQdKD0uOz1+sps2m5RFm5apuNzo+d71d3eIjEsqp+JASFuTq8p6n8KoqYGI5p96DDNjkLhWKyhGFkjPKC/C1JBAqp/xFgk2yIgCOKJp/gr/uGiTaKM/ltusV921cAc9NCkIkxCimYegKH2wshYRexs0KldzvksnwWqjUJ6xZDCpPRcO629iflWX93un4xnXK7brVEXXd+ePgL++h359i2d/rJPSJ8xaLxfKf+QLgIVsJpJiq2AAAAABJRU5ErkJggg==","orcid":"","institution":"Royal Adelaide Hospital","correspondingAuthor":true,"prefix":"","firstName":"Michele","middleName":"","lastName":"De Sciscio","suffix":""},{"id":433304105,"identity":"d5af3a72-2d22-4ccc-9bbe-81ec5924cbba","order_by":1,"name":"Robert V Bryant","email":"","orcid":"","institution":"Queen Elizabeth Hospital","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"V","lastName":"Bryant","suffix":""},{"id":433304106,"identity":"25dc38a6-f06e-4196-9386-629a143d76d9","order_by":2,"name":"Sarah Haylock-Jacobs","email":"","orcid":"","institution":"BiomeBank","correspondingAuthor":false,"prefix":"","firstName":"Sarah","middleName":"","lastName":"Haylock-Jacobs","suffix":""},{"id":433304107,"identity":"462bdfe6-ca16-4f40-bd1b-b74d90583d70","order_by":3,"name":"Alice S Day","email":"","orcid":"","institution":"Queen Elizabeth Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alice","middleName":"S","lastName":"Day","suffix":""},{"id":433304109,"identity":"fdbe9871-da18-4b5c-a28c-91f815975a83","order_by":4,"name":"William Pitchers","email":"","orcid":"","institution":"BiomeBank","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Pitchers","suffix":""},{"id":433304110,"identity":"8f782a3d-f5aa-49b5-a58f-15e1b113d58b","order_by":5,"name":"Robert Iansek","email":"","orcid":"","institution":"Clinical Research Centre for Movement Disorders \u0026 Gait","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Iansek","suffix":""},{"id":433304111,"identity":"6a9c9e49-10e9-44fa-93fa-59faf785a998","order_by":6,"name":"Samuel P Costello","email":"","orcid":"","institution":"BiomeBank","correspondingAuthor":false,"prefix":"","firstName":"Samuel","middleName":"P","lastName":"Costello","suffix":""},{"id":433304112,"identity":"58492021-8054-425f-855a-9e76a0936d2d","order_by":7,"name":"Thomas E Kimber","email":"","orcid":"","institution":"Royal Adelaide Hospital","correspondingAuthor":false,"prefix":"","firstName":"Thomas","middleName":"E","lastName":"Kimber","suffix":""}],"badges":[],"createdAt":"2025-03-09 20:08:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6190300/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6190300/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41531-025-01061-5","type":"published","date":"2025-07-09T15:57:16+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79562134,"identity":"bd3f53bf-f47b-4c56-b2fd-396a92f0e889","added_by":"auto","created_at":"2025-03-31 08:55:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":162331,"visible":true,"origin":"","legend":"\u003cp\u003eSelf-reported safety, acceptability, and tolerability of FMT across 3 timepoints in 12 patients with mild to moderate Parkinson’s Disease assessed using a 100-point visual analogue scale. FMT, Faecal Microbiota Transplant.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6190300/v1/046183a3d3be329e57ee6222.png"},{"id":79562135,"identity":"b5fa287b-ebc8-432c-a85e-8f799be17f21","added_by":"auto","created_at":"2025-03-31 08:55:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":180466,"visible":true,"origin":"","legend":"\u003cp\u003eBoxplots showing changes in motor and non-motor symptoms post FMT in patients with mild to moderate Parkinson’s Disease. UPDRS, Unified Parkinson’s Disease Rating Scale\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6190300/v1/0f3f8fd05a1c1e32ee6dbb63.png"},{"id":79562141,"identity":"3f347e6d-9400-40de-adcf-7fc52dd3e181","added_by":"auto","created_at":"2025-03-31 08:55:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":192370,"visible":true,"origin":"","legend":"\u003cp\u003eSelf-reported assessments of non-motor symptoms at 2- and 6-months post FMT compared with baseline. GDS-SF, Geriatric Depression Scale Short Forms; PDQ-39, Parkinson’s Disease Questionnaire; PD NMS, Parkinson’s Disease Non-Motor Symptoms Scale; PFS-16, Parkinson’s Disease Fatigue Scale; PDDS-2 Parkinson’s Disease Sleep Scale\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6190300/v1/848f160687bd2b72ce960728.png"},{"id":86699471,"identity":"0e1fdea5-1c64-40fe-be24-379a6399bcb2","added_by":"auto","created_at":"2025-07-14 16:10:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1049751,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6190300/v1/553a68f6-ae09-411e-a9dc-aa573b9e97bc.pdf"}],"financialInterests":"Competing interest reported. RV Bryant and SP Costello are shareholders in BiomeBank. However, the research was performed in keeping with good clinical practice with appropriate governance and oversight (including a safety monitoring board) to mitigate this conflict.","formattedTitle":"Faecal Microbiota Transplant in Parkinson's Disease: Pilot Study to Establish Safety \u0026 Tolerability","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eParkinson\u0026rsquo;s Disease (PD) is characterized by the accumulation of abnormal alpha-synuclein isoforms in neurons, causing dysfunction and cell death (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Disease progression is thought to result from the cell-to-cell transmission of alpha-synucleinopathy, leading to neurodegeneration (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The hallmark motor symptoms\u0026mdash;tremor, rigidity, and bradykinesia\u0026mdash;reflect neurodegeneration in central nervous system (CNS) motor circuits. However, evidence suggests that alpha-synuclein pathology begins in non-CNS neurons, such as those in the gut, years before affecting CNS neurons (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe gut is increasingly recognized as a key area in PD research. Alpha-synucleinopathy affects enteric neurons early, often causing constipation as a prodromal symptom (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Additionally, the vagus nerve may facilitate the spread of alpha-synucleinopathy from the gut to the CNS, with reduced PD risk in individuals who have undergone vagotomy and increased risk in those with inflammatory bowel disease (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This has led to growing interest in the role of gut microbiota in PD pathogenesis. Studies show that PD patients have altered microbiota, including higher levels of pro-inflammatory bacteria, lower levels of anti-inflammatory bacteria, and reduced microbial diversity (\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Though the exact link between gut dysbiosis and PD remains unclear, it may involve increased gut permeability and alpha-synuclein seeding in enteric neurons (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Moreover, microbiota composition correlates with motor and non-motor symptom severity and responses to dopaminergic treatments (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eFecal Microbiota Transplantation (FMT) is emerging as a potential therapy to modulate the gut microbiota in PD. Parkinson\u0026rsquo;s Disease mouse models have shown that FMT with healthy human-derived microbes improves motor function and protects against dopaminergic neuronal death (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). However, human studies on FMT's safety and efficacy are limited to short-term trials (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThis study aims to assess the safety and tolerability of an extended 6-month FMT course in mild to moderate PD patients. We will also evaluate the impact of FMT on daily OFF time, motor and non-motor symptoms, quality of life, and changes in gut microbiota composition and function.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Participants\u003c/h2\u003e \u003cp\u003eTwelve participants aged over 30 with a history of PD were recruited for this pilot study between June 2021 and November 2022. Key inclusion criteria were: (i) diagnosis of idiopathic PD for \u0026le;\u0026thinsp;10 years, as per the UK Parkinson's Disease Society Brain Bank criteria; (ii) a positive dopaminergic response, defined by a\u0026thinsp;\u0026ge;\u0026thinsp;33% reduction in Movement Disorders Society-Unified Parkinson\u0026rsquo;s Disease Rating Scale (MDS-UPDRS) III motor score between OFF and ON-dopaminergic medication states; and (iii) motor fluctuations with at least 2 hours of daily OFF time on at least two consecutive days. Subjects with mild cognitive impairment (Montreal Cognitive Assessment score\u0026thinsp;\u0026lt;\u0026thinsp;26) were excluded. Participants were required to maintain stable PD therapy for 30 days before and throughout the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eStudy Design\u003c/h3\u003e\n\u003cp\u003eThis was a prospective open-label, single centre study conducted by the Neurology and Gastroenterology Units of the Central Adelaide Local Health Network, Adelaide, Australia. Subjects underwent clinical assessment at baseline (pre-FMT), and at 2- and 6-months post FMT treatment commencement.\u003c/p\u003e\n\u003ch3\u003eFMT Treatment Regimen\u003c/h3\u003e\n\u003cp\u003eFMT enemas were sourced from Biomebank, a Therapeutic Goods Administration (TGA)-accredited provider based in South Australia (ARTG #399066). The FMT donor screening, collection, and manufacturing followed the standards outlined in Therapeutic Goods Order No. 105 \u0026ndash; Standards for FMT (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). The FMT was administered by a clinical nurse as a 50mL enema containing 12.5g of donor faeces. Subjects were instructed to retain the FMT for at least 30 minutes in the right lateral position. The intervention consisted of an induction phase with 6 donor FMT enemas over 8 weeks (weeks 0, 1, 2, 3, 5, 7), followed by a maintenance phase with 4 monthly donor FMT enemas over 4 months (months 3, 4, 5, 6), totalling 6 months of FMT therapy.\u003c/p\u003e\n\u003ch3\u003eStudy Assessments\u003c/h3\u003e\n\u003cp\u003eDaily OFF time was measured using Hauser motor diaries, completed by subjects for 48 consecutive hours. Subjects rated their motor state every half hour as \u0026ldquo;on without dyskinesia,\u0026rdquo; \u0026ldquo;on with non-troublesome dyskinesia,\u0026rdquo; \u0026ldquo;on with troublesome dyskinesia,\u0026rdquo; \u0026ldquo;off,\u0026rdquo; or \u0026ldquo;asleep.\u0026rdquo; Daytime ratings were contemporaneous, and overnight scores were made retrospectively.\u003c/p\u003e \u003cp\u003eSubjects were assessed using the Movement Disorder Society Unified Parkinson\u0026rsquo;s Disease Rating Scale (MDS-UPDRS) and the modified Hoehn and Yahr Scale. The MDS-UPDRS includes 4 domains: Part I (non-motor aspects of daily living), Part II (motor aspects of daily living), Part III (motor examination), and Part IV (motor complications).\u003c/p\u003e \u003cp\u003eSubjects attended baseline visits in the \u0026ldquo;OFF medication\u0026rdquo; state after overnight withdrawal of dopaminergic medication. The MDS-UPDRS Part III score was assessed in both \u0026ldquo;OFF\u0026rdquo; and \u0026ldquo;ON\u0026rdquo; medication states, approximately 1 hour after the usual morning dose of dopaminergic medication. For the 2- and 6-month visits, no pre-visit motor state stipulation was required. Motor examinations were performed by a single movement disorders specialist.\u003c/p\u003e \u003cp\u003eSafety and tolerability were monitored through adverse event reporting, patient experience questionnaires, and visual analogue scales. Subjects completed an adverse event questionnaire at each visit. Subjects completed a 2-point Likert scale questionnaire at each visit rating FMT\u0026rsquo;s acceptability, tolerability, and safety based on preconceived opinions and during treatment. Six non-motor questionnaires were completed, including the Geriatric Depression Scale Short Form (GDS-SF), Parkinson\u0026rsquo;s Disease Questionnaire (PDQ-39), Parkinson\u0026rsquo;s Disease Non-Motor Symptoms Scale (PD NMS), Parkinson\u0026rsquo;s Disease Fatigue Scale (PFS-16), Beck Depression Inventory, and Parkinson\u0026rsquo;s Disease Sleep Scale (PDSS-2). Across the study, subjects also reported subjective changes in motor symptoms, falls, constipation, and cognitive function. Bowel function was assessed using a 7-day diary, and microbiome analysis was performed at all timepoints. Constipation was defined by the Rome IV criteria for Bowel Disorders.\u003c/p\u003e \u003cp\u003eSubjects received dietary education from an academic dietitian at -14 days pre-FMT and at 2- and 6-month visits. They completed a 3-day weighed food diary, and data were analysed for energy, macronutrients, fibre, and micronutrients.\u003c/p\u003e \u003cp\u003eA Safety Review Committee (SRC) comprising experts in gastroenterology (RB) and neurology (TK, MD) was established to ensure participant safety.\u003c/p\u003e\n\u003ch3\u003eMicrobiome Analysis\u003c/h3\u003e\n\u003cp\u003eStool samples were collected in OMNIGene gut tubes (DNA Genotek) and sent for shotgun metagenomic sequencing at a depth of 40M 150bp paired-end reads on a DNBseq NanoBall platform.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Methods\u003c/h2\u003e \u003cp\u003eData are presented as mean (\u0026plusmn;\u0026thinsp;standard deviation) unless otherwise noted. Comparisons were analysed using a mixed-effects model to account for missing data, with Tukey\u0026rsquo;s multiple comparisons tests to compare timepoints. A p-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Dietary data were analysed using one-way ANOVA for normally distributed data. Statistical analyses were performed with GraphPad Prism version 10.0.2. A convenience sample size was used for this pilot study.\u003c/p\u003e \u003cp\u003eMicrobial makeup was profiled using standard bioinformatics tools (MetaPhlan V4), and microbiome analysis was conducted at BiomeBank, Australia to assess species richness, evenness (Pilou index), and alpha diversity (Shannon index). Microbiome indices were analyzed using a mixed-effects model with Tukey\u0026rsquo;s tests. Missing stool samples and questionnaires were handled with appropriate statistical methods.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003ePatient Characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 12 subjects (8 females, 4 males; mean age 69.5 years) received FMT treatment, Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The mean disease duration was 6.9 years, and all were on L-dopa therapy\u0026thinsp;\u0026plusmn;\u0026thinsp;adjunctive dopaminergic treatments, with a mean daily L-dopa equivalent dose of 684mg (range 100-1300mg). Key clinical markers of PD severity included: (i) daily OFF time (mean 4.8 hrs/24hrs, SD 2.2), (ii) UPDRS Part 3 in the OFF state (mean 28.3, SD 12.5) and ON state (mean 12.7, SD 8.3), and (iii) total UPDRS score (mean 42.8, SD 15.5). Constipation was reported in 58% of patients, with 9 of 12 subjects (75%) meeting the Rome IV criteria for functional constipation based on baseline 7-day bowel diaries.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1:\u003c/strong\u003e Patient Demographics and Baseline Values\u0026nbsp;\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"595\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBaseline Characteristics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e\u003cstrong\u003en=12\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eMale Patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e8 (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eAge at enrolment (years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e69.5 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eAge at diagnosis (years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e62.6 (5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e25.0 (5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eDisease duration at enrolment, (years)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e6.9 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eMedications\u0026nbsp;\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eL-dopa equivalent daily dose (mg)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eDopamine agonist\u003c/li\u003e\n \u003cli\u003eMonoamine oxidase inhibitors\u003c/li\u003e\n \u003cli\u003eCOMT inhibitors\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e684 (431)\u003c/p\u003e\n \u003cp\u003e8 (67%)\u003c/p\u003e\n \u003cp\u003e7 (58%)\u003c/p\u003e\n \u003cp\u003e4 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eComorbidities\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eDiabetes\u003c/li\u003e\n \u003cli\u003eHypertension\u003c/li\u003e\n \u003cli\u003eDepression\u003c/li\u003e\n \u003cli\u003eAnxiety\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2 (17 %)\u003c/p\u003e\n \u003cp\u003e3 (25 %)\u003c/p\u003e\n \u003cp\u003e4 (33 %)\u003c/p\u003e\n \u003cp\u003e5 (42 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eParkinson\u0026rsquo;s symptoms\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eTremor\u003c/li\u003e\n \u003cli\u003eRigidity\u003c/li\u003e\n \u003cli\u003eAkinesia/Bradykinesia\u003c/li\u003e\n \u003cli\u003eFreezing of gait\u003c/li\u003e\n \u003cli\u003eConstipation\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e10 (83 %)\u003c/p\u003e\n \u003cp\u003e11 (92 %)\u003c/p\u003e\n \u003cp\u003e12 (100 %)\u003c/p\u003e\n \u003cp\u003e3 (25 %)\u003c/p\u003e\n \u003cp\u003e7 (58 %)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eMontreal Cognitive Assessment\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e27.3 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 57.1429%;\"\u003e\n \u003cp\u003eParkinson\u0026rsquo;s Disease Severity Metrics\u003c/p\u003e\n \u003cul\u003e\n \u003cli\u003eUPDRS 1\u003c/li\u003e\n \u003cli\u003eUPDRS 2\u003c/li\u003e\n \u003cli\u003eUPDRS 4\u003c/li\u003e\n \u003cli\u003eUPDRS 3: OFF-state\u003c/li\u003e\n \u003cli\u003eUPDRS 3: ON-state\u003c/li\u003e\n \u003cli\u003eHauser Motor Diary (OFF time/24hrs)\u003c/li\u003e\n \u003c/ul\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 42.8571%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2.3 (1.6)\u003c/p\u003e\n \u003cp\u003e21.4 (8.0)\u003c/p\u003e\n \u003cp\u003e6.3 (1.8)\u003c/p\u003e\n \u003cp\u003e28.3 (12.5)\u003c/p\u003e\n \u003cp\u003e12.7 (8.3)\u003c/p\u003e\n \u003cp\u003e4.8 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eData expressed as either mean (SD), or number of patients (%). BMI=Body Mass Index; COMT=catechol-O-methyltransferase; UPDRS = Unified Parkinson\u0026rsquo;s Disease Rating Scale.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e* Constipation determined according to the Rome IV Criteria for Colonic Disorders\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003ePrimary Endpoints\u003c/h2\u003e\n \u003cdiv id=\"Sec12\" class=\"Section3\"\u003e\n \u003ch2\u003eSafety \u0026amp; Tolerability\u003c/h2\u003e\n \u003cp\u003eAll subjects who received at least one dose of FMT were included in the safety analysis. Eleven of 12 subjects (92%) completed the full 6-month treatment course. One serious adverse event (SAE) occurred: a subject was hospitalized with worsening motor symptoms after 2 months of treatment and withdrew from the study. The SAE was deemed unlikely to be related to FMT, as the subject had a history of steady functional decline prior to enrolment.\u003c/p\u003e\n \u003cp\u003eGastrointestinal adverse events were reported by 10 of 12 subjects (83%) as \u0026lsquo;probably\u0026rsquo; or \u0026lsquo;definitely\u0026rsquo; related to FMT, Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. These events were transient and mild, mostly occurring during the induction phase. No treatments were withheld due to adverse events. The most common adverse events were increased flatulence (50%), abdominal pain (42%), constipation (42%), and bloating (42%).\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eSelf-reported adverse events throughout 6 months of therapy deemed \u0026ldquo;probably\u0026rdquo; or \u0026ldquo;definitely\u0026rdquo; related to FMT\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAdverse event\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNumber of Patients (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBloating\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (42%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbdominal pain/cramping\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiarrhoea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (25%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConstipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (58%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIncreased flatulence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6 (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eUsing a 100-point visual analogue scale, most patients rated the acceptability and safety of FMT highly, with scores above 70/100 in 11 of 12 patients at both 2 and 6 months, Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003eSecondary Endpoints\u003c/h2\u003e\n \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e\n \u003ch2\u003eEfficacy of FMT on Motor Function\u003c/h2\u003e\n \u003cp\u003eThe mean self-reported daily OFF-time (averaged over 48 hours) was 4.8 hours/day (SD 2.2) at baseline and reduced to 3.8 hours/day (SD 1.8) after 2 months (p\u0026thinsp;=\u0026thinsp;0.58). However, this reduction was not sustained, with daily OFF-time returning to baseline levels by 6 months (4.4 hours/day, SD 2.8), Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. There was no significant change in UPDRS-Part IV scores, assessing motor complications, from baseline (6.3, SD 1.8) to 2 months (6.7, SD 1.8) and 6 months (5.6, SD 3.0) (p\u0026thinsp;=\u0026thinsp;0.49).\u003c/p\u003e\n \u003cp\u003eMost subjects (7/12) attended their 2- and 6-month reviews in a motor ON-state, allowing comparisons of ON-state MDS-UPDRS III (motor examination) scores across all three timepoints. While there was no improvement in these scores (baseline 9.4, SD 5.2; 2 months 9.7, SD 6.2; 6 months 9.7, SD 6.2; p\u0026thinsp;=\u0026thinsp;0.873), there was also no deterioration in the mean MDS-UPDRS III score over the 6-month treatment period, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003eEfficacy of FMT on Non-Motor Function\u003c/h2\u003e\n \u003cp\u003eAfter two months of FMT therapy, there was a non-significant reduction in the mean UPDRS Part I score (baseline 2.3, SD 1.6 vs 2 months 1.5, SD 1.5; p\u0026thinsp;=\u0026thinsp;0.336, 35% reduction) and UPDRS Part II score (baseline 21.4, SD 8.0 vs 2 months 17.9, SD 9.8; p\u0026thinsp;=\u0026thinsp;0.089, 16% reduction), Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. This reduction was maintained at 6 months for UPDRS Part II (17.1, SD 6.2), but UPDRS Part I showed regression towards baseline (1.8, SD 1.6).\u003c/p\u003e\n \u003cp\u003eThere was a statistically significant reduction in PDQ-39 scores between baseline and 2 months (34.7, SD 15.8 vs 25.3, SD 13.2; p\u0026thinsp;=\u0026thinsp;0.032) and a trend towards a reduction in NMSQ scores (9.5, SD 4.3 vs 7.7, SD 3.4; p\u0026thinsp;=\u0026thinsp;0.163), Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. However, these improvements were not maintained at 6 months. No statistically significant changes were observed in PFS-16, PDSS-2, BDIS, GDS, or PDSS-2 scores after 2 or 6 months of treatment.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\n \u003ch2\u003eEfficacy of FMT on Bowel Function\u003c/h2\u003e\n \u003cp\u003eThere was no improvement in bowel-related symptoms, as assessed by the 7-day bowel diary, after 2 or 6 months of FMT therapy. However, fewer subjects met the Rome IV criteria for functional constipation at 6 months post-treatment (baseline 9/12 [75%] vs 6 months 7/11 [64%]).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\n \u003ch2\u003eDietary optimisation and adequacy during FMT Therapy\u003c/h2\u003e\n \u003cp\u003eBefore receiving FMT, subjects\u0026apos; habitual diets were inadequate in dietary fibre and resistant starch, with a higher total protein intake. After individualized dietary advice, there was a trend toward increased dietary fiber at 8 weeks (mean intake 28.2g/d\u0026thinsp;\u0026plusmn;\u0026thinsp;9.98g/d), but this was not sustained at 24 weeks (24.7g/d\u0026thinsp;\u0026plusmn;\u0026thinsp;9.55g/d). Three subjects (27%) declined to modify their diet, and three (27%) chose to follow a gluten-free diet.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\n \u003ch2\u003eMicrobiome Changes with FMT Therapy\u003c/h2\u003e\n \u003cp\u003eThere was no difference in alpha diversity (Shannon index), richness, or evenness (Pilou index) of the gut microbiome from baseline in patients treated with FMT for 2 and 6 months. While minor changes were observed in some individual patients, most reverted to baseline by month 6, and aggregated results were non-significant, indicating no overall changes throughout the study.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis is the first study to evaluate the safety and tolerability of a 6-month FMT enema therapy course in patients with mild to moderate PD, showing that FMT is safe and well-tolerated. Apart from one serious adverse event (SAE) unrelated to FMT, adverse events were mild, self-limiting, and did not lead to treatment discontinuation. Most subjects rated FMT as safe and tolerable.\u003c/p\u003e \u003cp\u003eThese safety findings align with two recent studies that administered FMT to PD patients via oral capsules or colonic/nasointestinal routes. While gastrointestinal side effects were common, all were mild and self-limiting. FMT therapy for various gastrointestinal indications in 4,241 patients has been shown to be highly safe, with only mild or moderate adverse events (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough this study was not designed to assess efficacy, there was a significant improvement in QOL scores at 2 months post-FMT. Additionally, trends toward improvement were observed in non-motor scales, including the non-motor symptom questionnaire (NMSQ), UPDRS Parts I \u0026amp; II, and PDSS-2 scores, but these were not sustained at 6 months.\u003c/p\u003e \u003cp\u003eA trend toward improvement in motor symptoms was observed, with a reduction in self-reported OFF-time at 2 months (mean 4.8hrs/day at baseline vs. 3.8hrs/day at 2 months), corresponding to a 21% reduction. Although this improvement was not statistically significant or sustained at 6 months, motor impairment scores (Hauser diary OFF-time and ON-state MDS-UPDRS motor examination score) at 6 months were at or slightly improved compared to baseline. To our knowledge, this is the first study to assess the effects of FMT on daily OFF-time in PD, using the Hauser motor diary, which is increasingly favoured in PD to more accurately represent real-world motor dysfunction in daily life.\u003c/p\u003e \u003cp\u003eThe initial improvement in PDQ-39 and trend towards improvement in NMSQ scores, at 2 months, coinciding with the induction phase of therapy (weekly or fortnightly FMT enemas), suggests that more frequent dosing may be needed to sustain benefits. This aligns with a recent placebo-controlled study where greater improvement was seen with more frequent FMT dosing (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). However, another study showed significant improvement in non-motor symptoms with a single colonic or nasogastric FMT, suggesting a single dose may also be effective (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile no significant improvement in bowel symptoms (7-day bowel diary) was seen, a reduction in subjects meeting the Rome IV criteria for functional constipation was noted at 6 months (75% at baseline vs. 64% at 6 months). Previous studies have demonstrated improvements in constipation with FMT, including changes in bowel transit and motility index, potentially due to increased gut microbiome diversity. Our study did not show significant changes in alpha diversity, richness, or evenness of the gut microbiome, possibly due to the enema delivery method and frequency of dosing.\u003c/p\u003e \u003cp\u003eThis study has several limitations. It was an open-label, non-randomized pilot with a small sample size, limiting its ability to detect significant effects. Furthermore, despite regular dietetics input, many subjects maintained inadequate fibre and resistant starch intake, which may have affected FMT engraftment and minimized potential benefits. Finally, our study was a convenience sample of patients referred by their Movement Disorder Specialist, many of which were aware of FMT as a potential therapy for PD. Thus, our study may not be representative of the broader population of patients with PD. Despite these limitations, this pilot study suggests the potential clinical value of FMT in PD and justifies further investigation through larger, double-blind, placebo-controlled trials with oral, daily FMT dosing.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study demonstrated that a 6-month course of FMT for treating mild to moderate PD is safe and well-tolerated. FMT was associated with improvements in self-reported quality of life and trends toward reductions in daily OFF-time and multiple non-motor symptoms. However, these benefits were most apparent with more frequent FMT dosing, with regression toward baseline observed with less frequent therapy. The findings are promising and support further investigation into FMT as a novel and safe treatment option for PD management.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eETHICAL COMPLIANCE \u0026nbsp;STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eProcedures involving experiments on human subjects are done in accordance with the ethical standards of the Committee on Human Experimentation of the institution in which the experiments were done or in accord with the Helsinki Declaration of 1975. All participants provided written consent to participate in this study. The study was approved by Central Adelaide Local Health Network Human Research Ethics Committee (# 2021/HRE00012).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was funded by the Hospital Research Foundation Group (2021/23-QA253).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe acknowledge the efforts of the Queen Elizabeth Hospital Inflammatory Bowel Disease Clinical Trial Nurses who were involved in the administration of FMT and post-treatment care of patients throughout the duration of the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eDATA SHARING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJankovic J, Tan EK (2020) Parkinson\u0026rsquo;s disease: etiopathogenesis and treatment. \u003cem\u003eJournal of Neurology, Neurosurgery \u0026amp; Psychiatry\u003c/em\u003e 91, 795-808.\u003c/li\u003e\n\u003cli\u003eFitzgerald E, Murphy S, Martinson HA (2019) Alpha-Synuclein Pathology and the Role of the Microbiota in Parkinson\u0026apos;s Disease. \u003cem\u003eFront Neurosci\u003c/em\u003e. 24, 13:369. doi: 10.3389/fnins.2019.00369. PMID: 31068777; PMCID: PMC6491838.\u003c/li\u003e\n\u003cli\u003eLiu J, Xu F, Nie Z, Shao L (2020) Gut Microbiota Approach-A New Strategy to Treat Parkinson\u0026apos;s Disease. \u003cem\u003eFront Cell Infect Microbiol\u003c/em\u003e. 22;10:570658. doi: 10.3389/fcimb.2020.570658. PMID: 33194809; PMCID: PMC7643014.\u003c/li\u003e\n\u003cli\u003eStokholm MG, Danielsen EH, Hamilton-Dutoit SJ, Borghammer P (2016) Pathological \u0026alpha;-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. \u003cem\u003eAnn Neurol\u003c/em\u003e 79, 940\u0026ndash;949. \u003c/li\u003e\n\u003cli\u003eBraak, H., Rüb, U., Gai, W., and Del Tredici, K. (2003) Idiopathic Parkinson\u0026rsquo;s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. \u003cem\u003eJ. Neural Transm\u003c/em\u003e. 110, 517\u0026ndash;536. doi: 10.1007/s00702-002-0808-2\u003c/li\u003e\n\u003cli\u003eScheperjans, F., Aho, V., Pereira, P. A., Koskinen, K., Paulin, L., Pekkonen, E., et al. (2015). Gut microbiota are related to Parkinson\u0026rsquo;s disease and clinical phenotype. \u003cem\u003eMov. Disord\u003c/em\u003e. 30, 350\u0026ndash;358. doi: 10.1002/mds.26069\u003c/li\u003e\n\u003cli\u003eSchwiertz, A. et al (2018) Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson\u0026rsquo;s disease. \u003cem\u003eParkinsonism Relat. Disord\u003c/em\u003e. https:// doi.org/10.1016/j.parkreldis.2018.02.022 \u003c/li\u003e\n\u003cli\u003eUnger, M.M.,Spiegel, J.,Dillmann, K (2016) Short chain fatty acids and gut microbiota differ between patients with Parkinson\u0026apos;s disease and age-matched controls. \u003cem\u003eParkinsonism Relat Disord \u003c/em\u003e32, 66\u0026ndash;72. \u003c/li\u003e\n\u003cli\u003eBaldini F, Hertel J, Sandt E, Thinnes CC, Neuberger-Castillo L, Pavelka L, et al (2020) Parkinson\u0026rsquo;s disease-associated alterations of the gut microbiome predict disease- relevant changes in metabolic functions. \u003cem\u003eBMC Biol\u003c/em\u003e 18:62. doi: 10.1101/691030 \u003c/li\u003e\n\u003cli\u003eSun MF, Zhu YL, Zhou ZL, Jia XB, Xu YD, Yang Q, et al (2018) Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson\u0026rsquo;s disease mice: gut microbiota, glial reaction and TLR4/TNF-alpha signaling pathway. \u003cem\u003eBrain Behav Immun\u003c/em\u003e. 70, 48\u0026ndash;60. doi: 10.1016/j.bbi.2018.02.005 \u003c/li\u003e\n\u003cli\u003eDuPont HL, Suescun J, Jiang ZD, Brown EL, Essigmann HT, Alexander AS, DuPont AW, Iqbal T, Utay NS, Newmark M, Schiess MC (2023) Fecal microbiota transplantation in Parkinson\u0026apos;s disease-A randomized repeat-dose, placebo-controlled clinical pilot study. \u003cem\u003eFront Neurol\u003c/em\u003e. 2;14:1104759. doi: 10.3389/fneur.2023.1104759. PMID: 36937520; PMCID: PMC10019775.\u003c/li\u003e\n\u003cli\u003eXue LJ, Yang XZ, Tong Q, Shen P, Ma SJ, Wu SN, Zheng JL, Wang HG (2020) Fecal microbiota transplantation therapy for Parkinson\u0026apos;s disease: A preliminary study. \u003cem\u003eMedicine\u003c/em\u003e\u003cem\u003e(Baltimore)\u003c/em\u003e. 28;99(35):e22035. doi: 10.1097/MD.0000000000022035. PMID: 32871960; PMCID: PMC7458210.\u003c/li\u003e\n\u003cli\u003eTucker EC, Haylock-Jacobs S, Rapaic M, Dann LM, Bryant RV, Costello SP (2023) Stool donor screening within a Therapeutic Goods Administration compliant donor screening program for fecal microbiota transplantation. \u003cem\u003eJGH Open\u003c/em\u003e. 21;7(3):172-177. doi: 10.1002/jgh3.12874. PMID: 36968571; PMCID: PMC10037028.\u003c/li\u003e\n\u003cli\u003eMarcella C, Cui B, Kelly CR, Ianiro G, Cammarota G, Zhang F (2021) Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020. \u003cem\u003eAP\u0026amp;T\u003c/em\u003e. 53:1 33-42. https://doi.org/10.1111/apt.16148 \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"npj-parkinsons-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjparkd","sideBox":"Learn more about [npj Parkinson's Disease](http://www.nature.com/npjparkd/)","snPcode":"41531","submissionUrl":"https://submission.springernature.com/new-submission/41531/3","title":"npj Parkinson's Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6190300/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6190300/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThere is growing evidence that differences exist in the gut microbiota of patients with Parkinson\u0026rsquo;s Disease (PD) compared with health controls, and so treatment with Faecal Microbiota Transplantation (FMT) may provide a novel approach towards altering disease progression and response to treatment. We performed a pilot study looking at the safety and tolerability of FMT, its effect on the microbiome, and improvement of symptoms in PD. This was an open label study wherein 12 patients with mild to moderate PD were administered FMT via enema for 6 months. The primary objectives were safety and tolerability of therapy as well as changes in motor and non-motor symptoms of PD. FMT administered as liquid enema was safe and well tolerated, associated with mild and self-resolving gastrointestinal symptoms. We found no significant change in motor outcomes post FMT however showed a trend towards improvement in daily OFF time after 2 months of treatment. We found no significant improvement in non-motor symptoms of PD after 6-months of FMT, however showed improvement in quality of life and non-motor symptom scores at 2 months as well as a trend towards improvement in parts 1 and 2 of the MDS-UPDRS. All improvements regressed back to baseline after 6 months of treatment. The administration of FMT over an extended 6-month period for the treatment of mild to moderate PD is safe and tolerable. FMT was associated with a transient reduction in daily motor OFF time as well as multiple self-reported non-motor symptoms.\u003c/p\u003e","manuscriptTitle":"Faecal Microbiota Transplant in Parkinson's Disease: Pilot Study to Establish Safety \u0026amp; Tolerability","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 08:55:11","doi":"10.21203/rs.3.rs-6190300/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-14T05:52:11+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-09T22:40:11+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-20T12:26:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"334453548470741787542481515248455752830","date":"2025-03-20T11:08:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"18679821759143392019706440151795238612","date":"2025-03-19T15:30:56+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-18T14:33:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-03-17T14:10:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-17T04:58:34+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Parkinson's Disease","date":"2025-03-09T20:05:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-parkinsons-disease","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjparkd","sideBox":"Learn more about [npj Parkinson's Disease](http://www.nature.com/npjparkd/)","snPcode":"41531","submissionUrl":"https://submission.springernature.com/new-submission/41531/3","title":"npj Parkinson's Disease","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7b33991a-a328-41b0-9faa-4dfd19ca719c","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":46138512,"name":"Health sciences/Diseases/Neurological disorders/Movement disorders/Parkinsons disease"},{"id":46138513,"name":"Biological sciences/Neuroscience/Motor control/Basal ganglia"}],"tags":[],"updatedAt":"2025-07-14T16:04:58+00:00","versionOfRecord":{"articleIdentity":"rs-6190300","link":"https://doi.org/10.1038/s41531-025-01061-5","journal":{"identity":"npj-parkinsons-disease","isVorOnly":false,"title":"npj Parkinson's Disease"},"publishedOn":"2025-07-09 15:57:16","publishedOnDateReadable":"July 9th, 2025"},"versionCreatedAt":"2025-03-31 08:55:11","video":"","vorDoi":"10.1038/s41531-025-01061-5","vorDoiUrl":"https://doi.org/10.1038/s41531-025-01061-5","workflowStages":[]},"version":"v1","identity":"rs-6190300","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6190300","identity":"rs-6190300","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}